Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAZRUW3)

DOT Name Interferon regulatory factor 2 (IRF2)
Synonyms IRF-2
Gene Name IRF2
Related Disease
Lung carcinoma ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Atopic dermatitis ( )
Autoimmune disease ( )
Breast carcinoma ( )
Coeliac disease ( )
Colorectal carcinoma ( )
Dermatitis ( )
Hepatitis C virus infection ( )
Herpes simplex infection ( )
Leukemia ( )
Lung cancer ( )
Medulloblastoma ( )
Neoplasm ( )
Neuroblastoma ( )
Osteoporosis ( )
Pancreatic tumour ( )
Psoriasis ( )
Sjogren syndrome ( )
Skin disease ( )
Systemic lupus erythematosus ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
B-cell lymphoma ( )
Epithelial ovarian cancer ( )
Metastatic malignant neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Small lymphocytic lymphoma ( )
Asthma ( )
Bone osteosarcoma ( )
Colon cancer ( )
Colon carcinoma ( )
Coronary heart disease ( )
Gastric cancer ( )
Kaposi sarcoma ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
UniProt ID
IRF2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00605
Sequence
MPVERMRMRPWLEEQINSNTIPGLKWLNKEKKIFQIPWMHAARHGWDVEKDAPLFRNWAI
HTGKHQPGVDKPDPKTWKANFRCAMNSLPDIEEVKDKSIKKGNNAFRVYRMLPLSERPSK
KGKKPKTEKEDKVKHIKQEPVESSLGLSNGVSDLSPEYAVLTSTIKNEVDSTVNIIVVGQ
SHLDSNIENQEIVTNPPDICQVVEVTTESDEQPVSMSELYPLQISPVSSYAESETTDSVP
SDEESAEGRPHWRKRNIEGKQYLSNMGTRGSYLLPGMASFVTSNKPDLQVTIKEESNPVP
YNSSWPPFQDLPLSSSMTPASSSSRPDRETRASVIKKTSDITQARVKSC
Function
Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and represses those genes. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation.
Tissue Specificity Expressed throughout the epithelium of the colon. Also expressed in lamina propria.
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )
Interferon alpha/beta signaling (R-HSA-909733 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Pyroptosis (R-HSA-5620971 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung carcinoma DISTR26C Definitive Biomarker [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Arteriosclerosis DISK5QGC Strong Biomarker [3]
Atherosclerosis DISMN9J3 Strong Biomarker [3]
Atopic dermatitis DISTCP41 Strong Genetic Variation [4]
Autoimmune disease DISORMTM Strong Genetic Variation [5]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Coeliac disease DISIY60C Strong Altered Expression [7]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [8]
Dermatitis DISY5SZC Strong Biomarker [9]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [10]
Herpes simplex infection DISL1SAV Strong Genetic Variation [4]
Leukemia DISNAKFL Strong Biomarker [11]
Lung cancer DISCM4YA Strong Biomarker [12]
Medulloblastoma DISZD2ZL Strong Altered Expression [13]
Neoplasm DISZKGEW Strong Biomarker [14]
Neuroblastoma DISVZBI4 Strong Biomarker [15]
Osteoporosis DISF2JE0 Strong Biomarker [16]
Pancreatic tumour DIS3U0LK Strong Genetic Variation [17]
Psoriasis DIS59VMN Strong Genetic Variation [18]
Sjogren syndrome DISUBX7H Strong Altered Expression [19]
Skin disease DISDW8R6 Strong Biomarker [9]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [20]
Acute myelogenous leukaemia DISCSPTN moderate Altered Expression [21]
Advanced cancer DISAT1Z9 moderate Biomarker [22]
B-cell lymphoma DISIH1YQ moderate Altered Expression [23]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [24]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [8]
Ovarian cancer DISZJHAP moderate Biomarker [24]
Ovarian neoplasm DISEAFTY moderate Biomarker [24]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [23]
Asthma DISW9QNS Limited Biomarker [25]
Bone osteosarcoma DIST1004 Limited Altered Expression [26]
Colon cancer DISVC52G Limited Genetic Variation [27]
Colon carcinoma DISJYKUO Limited Genetic Variation [27]
Coronary heart disease DIS5OIP1 Limited Biomarker [28]
Gastric cancer DISXGOUK Limited Altered Expression [14]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [29]
Melanoma DIS1RRCY Limited Biomarker [1]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [30]
Osteosarcoma DISLQ7E2 Limited Altered Expression [26]
Pancreatic cancer DISJC981 Limited Biomarker [31]
Prostate cancer DISF190Y Limited Altered Expression [32]
Prostate carcinoma DISMJPLE Limited Altered Expression [32]
Stomach cancer DISKIJSX Limited Altered Expression [14]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Interferon regulatory factor 2 (IRF2). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Interferon regulatory factor 2 (IRF2). [42]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Interferon regulatory factor 2 (IRF2). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Interferon regulatory factor 2 (IRF2). [44]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Interferon regulatory factor 2 (IRF2). [34]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Interferon regulatory factor 2 (IRF2). [35]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Interferon regulatory factor 2 (IRF2). [36]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Interferon regulatory factor 2 (IRF2). [37]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Interferon regulatory factor 2 (IRF2). [38]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Interferon regulatory factor 2 (IRF2). [39]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Interferon regulatory factor 2 (IRF2). [40]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Interferon regulatory factor 2 (IRF2). [41]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Interferon regulatory factor 2 (IRF2). [45]
Rutin DMEHRAJ Investigative Rutin increases the expression of Interferon regulatory factor 2 (IRF2). [46]
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⏷ Show the Full List of 10 Drug(s)

References

1 Combination of Asiatic Acid and Naringenin Modulates NK Cell Anti-cancer Immunity by Rebalancing Smad3/Smad7 Signaling.Mol Ther. 2018 Sep 5;26(9):2255-2266. doi: 10.1016/j.ymthe.2018.06.016. Epub 2018 Jun 22.
2 Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.Alzheimers Dement. 2018 May;14(5):623-633. doi: 10.1016/j.jalz.2017.11.006. Epub 2017 Dec 20.
3 Loss of IRF2BP2 in Microglia Increases Inflammation and Functional Deficits after Focal Ischemic Brain Injury.Front Cell Neurosci. 2017 Jul 19;11:201. doi: 10.3389/fncel.2017.00201. eCollection 2017.
4 Genetic variants in interferon regulatory factor 2 (IRF2) are associated with atopic dermatitis and eczema herpeticum.J Invest Dermatol. 2012 Mar;132(3 Pt 1):650-7. doi: 10.1038/jid.2011.374. Epub 2011 Nov 24.
5 Type I interferons and autoimmunity: lessons from the clinic and from IRF-2-deficient mice.Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):379-91. doi: 10.1016/s1359-6101(02)00023-0.
6 The role of interferon regulatory factor-1 and interferon regulatory factor-2 in IFN-gamma growth inhibition of human breast carcinoma cell lines.J Interferon Cytokine Res. 2003 Sep;23(9):501-11. doi: 10.1089/10799900360708623.
7 Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease.Pediatr Res. 2003 Sep;54(3):312-8. doi: 10.1203/01.PDR.0000079184.70237.9C. Epub 2003 Jun 4.
8 Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes.Int J Cancer. 2019 Sep 15;145(6):1648-1659. doi: 10.1002/ijc.32196. Epub 2019 Feb 20.
9 IRF-2 haploinsufficiency causes enhanced imiquimod-induced psoriasis-like skin inflammation.J Dermatol Sci. 2018 Apr;90(1):35-45. doi: 10.1016/j.jdermsci.2017.12.014. Epub 2017 Dec 28.
10 Dysregulation of interferon regulatory factors impairs the expression of immunostimulatory molecules in hepatitis C virus genotype 1-infected hepatocytes.Gut. 2014 Apr;63(4):665-73. doi: 10.1136/gutjnl-2012-304377. Epub 2013 Jun 20.
11 The role of IRF1 and IRF2 transcription factors in leukaemogenesis.Curr Gene Ther. 2006 Oct;6(5):543-50. doi: 10.2174/156652306778520683.
12 MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer.Cell Death Dis. 2017 May 4;8(5):e2764. doi: 10.1038/cddis.2017.145.
13 Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and -2.Br J Cancer. 1998 Jun;77(12):2081-7. doi: 10.1038/bjc.1998.351.
14 IRF-2 Inhibits Gastric Cancer Invasion and Migration by Down-Regulating MMP-1.Dig Dis Sci. 2020 Jan;65(1):168-177. doi: 10.1007/s10620-019-05739-8. Epub 2019 Jul 26.
15 Interferon regulatory factor-2 physically interacts with NF-kappa B in vitro and inhibits NF-kappa B induction of major histocompatibility class I and beta 2-microglobulin gene expression in transfected human neuroblastoma cells.J Neuroimmunol. 1995 Dec 31;63(2):157-62. doi: 10.1016/0165-5728(95)00140-9.
16 Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics.Stem Cell Reports. 2017 Apr 11;8(4):947-960. doi: 10.1016/j.stemcr.2017.02.018. Epub 2017 Mar 23.
17 Interferon regulatory factor-2 point mutations in human pancreatic tumors.Int J Cancer. 2000 Sep 15;87(6):803-8.
18 Variation at the IRF2 gene and susceptibility to psoriasis in chromosome 4q-linked families.J Invest Dermatol. 2004 Mar;122(3):640-3. doi: 10.1046/j.0022-202X.2004.22135.x.
19 Expression of the immune regulator tripartite-motif 21 is controlled by IFN regulatory factors.J Immunol. 2013 Oct 1;191(7):3753-63. doi: 10.4049/jimmunol.1202341. Epub 2013 Aug 23.
20 Association of functional polymorphisms in interferon regulatory factor 2 (IRF2) with susceptibility to systemic lupus erythematosus: a case-control association study.PLoS One. 2014 Oct 6;9(10):e109764. doi: 10.1371/journal.pone.0109764. eCollection 2014.
21 IRF2-INPP4B-mediated autophagy suppresses apoptosis in acute myeloid leukemia cells.Biol Res. 2019 Mar 15;52(1):11. doi: 10.1186/s40659-019-0218-7.
22 Interferon regulatory factor 1 inactivation in human cancer.Biosci Rep. 2018 May 8;38(3):BSR20171672. doi: 10.1042/BSR20171672. Print 2018 Jun 29.
23 BAL1/ARTD9 represses the anti-proliferative and pro-apoptotic IFN-STAT1-IRF1-p53 axis in diffuse large B-cell lymphoma.J Cell Sci. 2013 May 1;126(Pt 9):1969-80. doi: 10.1242/jcs.118174. Epub 2013 Mar 13.
24 Intratumoral interferon regulatory factor (IRF)-1 but not IRF-2 is of relevance in predicting patient outcome in ovarian cancer.Int J Cancer. 2009 May 15;124(10):2353-60. doi: 10.1002/ijc.24214.
25 Genetic association of key Th1/Th2 pathway candidate genes, IRF2, IL6, IFNGR2, STAT4 and IL4RA, with atopic asthma in the Indian population.J Hum Genet. 2015 Aug;60(8):443-8. doi: 10.1038/jhg.2015.45. Epub 2015 May 21.
26 miR-18a-5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2.Oncol Lett. 2018 Sep;16(3):3150-3156. doi: 10.3892/ol.2018.9032. Epub 2018 Jun 27.
27 Interferon-signaling pathway: associations with colon and rectal cancer risk and subsequent survival.Carcinogenesis. 2011 Nov;32(11):1660-7. doi: 10.1093/carcin/bgr189. Epub 2011 Aug 22.
28 Integrated microRNAgene analysis of coronary artery disease based on miRNA and gene expression profiles.Mol Med Rep. 2016 Apr;13(4):3063-73. doi: 10.3892/mmr.2016.4936. Epub 2016 Feb 23.
29 ERK1/2 and MEK1/2 induced by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection.J Virol. 2005 Aug;79(16):10308-29. doi: 10.1128/JVI.79.16.10308-10329.2005.
30 Nasopharyngeal carcinoma super-enhancer-driven ETV6 correlates with prognosis.Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9683-9688. doi: 10.1073/pnas.1705236114. Epub 2017 Aug 22.
31 The roles of interferon regulatory factors 1 and 2 in the progression of human pancreatic cancer.Pancreas. 2014 Aug;43(6):909-16. doi: 10.1097/MPA.0000000000000116.
32 Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3.Cancer Res. 2014 May 1;74(9):2591-603. doi: 10.1158/0008-5472.CAN-13-1606. Epub 2014 Mar 7.
33 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
34 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
35 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
36 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
37 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
38 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
39 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
40 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
41 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
42 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
43 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
44 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
45 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
46 Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.